The discovery, development and commercialization of the 2-(2-imidazolin-2-yl) pyridines and quinolines as herbicidal agents has given new meaning to the term "weed control"; for within this series of compounds it has been found that some are broad-spectrum or total vegetation herbicides with activity in both herbaceous and woody plants. Others are highly selective weed control agents useful as weed control agents in the presence of crops. The broad-spectrum compounds have been widely accepted for use in cleaning industrial sites and rights-of-way for railroads and power lines while the selective herbicides are used extensively as weed control agents in the presence of soybeans, snapbeans, peas and alfalfa. Such acceptance has stirred the interest of many researchers in the field of agricultural chemistry and has led to development of a variety of synthetic routes to the preparation of the herbicidally active 2-(2-imidazolin-2-yl)pyridines and quinolines.
Several of these processes involve the preparation of 2,3-pyridinedicarboxylic acid anhydrides from 2,3-pyridinedicarboxylic acids, but methods for the preparation of the 2,3-pyridinedicarboxylic acids are rather limited and those processes that are available may be arduous, time-consuming or multi-step processes that are not entirely satisfactory.
For example, P. J. Wepplo in U.S. Pat. No. 4,460,776, describes the preparation of a 6-substituted-2,3-pyridinedicarboxylic acid diester and the hydrolysis of the diester to the corresponding diacid by reaction of the diester with strong base in the presence of alcohol. Thereafter, the reaction mixture is treated with a strong mineral acid, ice and an alcohol. The mixture is then cooled, diluted with a ketonic solvent, treated with solid sodium sulfate and filtered. The filtrate is concentrated, the residue triturated with ether and the diacid removed by filtration. Treatment of the diacid with acetic anhydride in the presence of dimethoxyethane and pyridine yields the 6-substituted-2,3-pyridinedicarboxylic acid anhydride which is further treated to obtain the herbicidal 6-substituted-2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid.
M. Los in U.S. Pat. No. 4,608,079 discloses the preparation of 3-chloro-4-methylphthalic acid from 3-chloro-N,N-diethyl-p-toluamide using butyl lithium in cyclohexane in the presence of anhydrous tetrahydrofuran and N,N,N.sup.1,N.sup.1 -tetramethylethylenediamine.
R. F. Doehner, Jr., in U.S. Pat. No. 4,723,011, discloses the preparation of substituted and disubstituted pyridine-2,3-dicarboxylate esters. However, the patentee also discloses the base hydrolysis of the diester described by Wepplo for the preparation of the substituted or disubstituted diacid, followed by conversion of the diacid to the anhydride. The anhydride is then reacted with an aminocarboxamide or aminothiocarboxamide to form the pyridine monoacid-diamide which is cyclized to the active substituted or disubstituted 2-(5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl)nicotinic acid.
Methods requiring the use of transition metal catalysts in oxidizing quinolines such as those described in German Patents 3,345,223 and 3,150,005; French Patent 2,193,820; and U.S. Pat. No. 3,829,432 are limited to the preparation of either the unsubstituted 2,3-pyridinedicarboxylic acid or to the preparation of those compounds which do not contain substituents which are also oxidized during the process. Additionally, an oxidative method for the preparation of 2,3-pyridinedicarboxylic acids is disclosed in U.S. Pat. No. 3,027,380 which describes the preparation of 5-fluoropyridine-2,3-dicarboxylic acid by the action of nascent or atomic oxygen on 3-fluoroquinoline; and British Patent Application 880,592 describes a method of preparing substituted and unsubstituted 2,3-pyridinedicarboxylic acids by ozonolysis of benzazines such as quinalidine, lepidine, carbostyril, 8-hydroxyquinoline and 2-aminoquinoline in the presence of a sufficient amount of a mineral acid such as nitric acid, sulfuric acid or phosphoric acid to form a salt of the benzazine.
Early reports describing the preparation of alkyl substituted 2,3-pyridinedicarboxylic acids by oxidative methods stemmed from interest in lepidine (4-methylquinoline).
S. Hoogeweff and W. A. van Dorp Chem. Ber. 13, 1639 reported that 4-methyl-2,3-pyridinedicarboxylic acid may be isolated from the stepwise oxidation of lepidine with permanganate.
C. Riedel, Chem. Ber. 16 1609-1616 citing the work of Hoogeweff and van Dorp, proposed in a like manner to conduct a reaction sequence of oxidizing .beta.-ethylbenzoquinoline to .beta.-ethylpyridine-2,3-carboxylic acid, followed by decarboxylation by distillation over calcium hydroxide to obtain .beta.-ethylpyridine which would, upon further oxidation yield .beta.-pyridinecarboxylic acid, as a method to confirm the position of the carboxlyic acid substituent.
Riedel reported that oxidation of .beta.-ethylbenzoquinoline with chromic acid yielded .beta.-benzoquinolinecarboxylic acid and that further oxidation of this compound with potassium permanganate under basic conditions yielded the corresponding pyridinetricarboxylic acid. Based upon this result, Riedel drew the conclusion that the difference in behavior of .beta.-ethylquinoline and lepidine was due to the difference in the length of the alkyl chain (ethyl vs methyl).
O. Doebner and W. van Miller Chem. Ber. 18, 1640-1646, commented on the conclusion drawn by Riedel, citing H. Weidel. Monatshefte F. Chem. 3 79 "who showed that, in the oxidation of cincholepidine with chromic acid instead of with potassium permanganate, it is not the benzene group but the methyl group that is attacked". Doebner and van Miller additionally demonstrated that the oxidation .beta.-methylquinoline with chromic acid also resulted in oxidation of the methyl group.
Support for the Doebner and van Miller publication has been evidenced by the potassium permanganate oxidation of 3-ethylquinoline under basic conditions (the conditions employed by Riedel for the subsequent oxidation .beta.-benzoquinolinecarboxylic acid to the corresponding pyridinetricarboxylic acid) to produce 5-ethylpyridine-2,3-dicarboxylic acid in 6 to 7% yields.
Recent oxidative methods which have been reported to be suitable for the preparation of 2,3-pyridinedicarboxylic acids containing substituents in the 4, 5 and 6 position of the pyridine ring include:
A. the preparation of 5-methylpyridine-2,3-dicarboxylic acid by nitric acid oxidation of 8-hydroxy-3-methylquinoline which was obtained by Skraup reaction of o-aminophenol with .alpha.-methylacraldehyde; V. Oakes and H. N. Rydon, J. Chem. Soc., 4433 (1956); and
B. the preparation of 4-methylpyridine-2,3-dicarboxylic acid, in 65% yield; 5-methylpyridine-2,3-dicarboxylic acid, in 50% yield; and 6-methylpyridine-2,3-dicarboxylic acid in 57% yield by the oxidation of the corresponding 4, 5 or 6 methyl 8-hydroxyquinoline with nitric acid and the preparation of 5-chloropyridine-2,3-dicarboxylic acid in 31% yield by the oxidation of 3-chloroquinoline with KMnO.sub.4 ; B. Blank, et al., J. Med. Chem., Vol 17, No. 10, 1065 (1974).
It has been shown that oxidation 3-ethyl-8-hydroxyquinoline (prepared in 39% yield by the Skraup reaction of o-aminophenol with 2-ethylacrolein), with nitric acid as described in the above publications yields: 5-ethyl-2,3-pyridinedicarboxylic acid having mp 146.degree.-147.degree. C. in 40% yield.
Like the processes of the patent art, the methods of synthesis of the 2,3-pyridine and quinolinedicarboxylic acids described in the literature are not entirely satisfactory for large scale commercial production.
It is therefore an object of the present invention to provide an effective and efficient method for the preparation of substituted and unsubstituted 2,3-pyridine and quinolinedicarboxylic acids.